The overall objective is to expand and develop the Simian Immunodeficiency Virus (SIV) model of human AIDS into new areas that are of interest to the Division of Research Resources. We have chosen the following areas for development; (1) the expansion of personnel and facilities to include pharmacologic capabilities that will allow the testing of potential therapeutic agents in SIV- infected rhesus macaques, (2) the introduction of SIV into a macaque group to study the dynamics of a controlled outbreak of SIV, and (3) examination of potentially new AIDS models by studying SIV infection, pathogenesis and carrier states as they occur naturally in wild-caught sooty mangabeys (Cercocebus arys) in Liberia West Africa and African green monkeys (AGMs) (Cercopithecus aethiops) in East Africa. For pharmacologic development we will construct a module in the first year which will be for housing infected animals or drug studies. In preparation for in vivo studies, we will simultaneously test nucleoside analogs in vitro for their activity against SIV. Initially we will limit ourselves to compounds that are under development by drug companies and have already shown some promise in vitro or in vivo against HIV. By coordinating our efforts with workers involved in HIV drug development, we hope to be able to test new drugs and ways to improve existing AIDS drug therapy by one year after the awarding of supplemental funds. Secondly, to better understand the natural history of SIV we will create an endemic infection in outdoor housed rhesus by inoculating some members of small groups with SIV. It is expected that the outdoor environment may broaden the spectrum of opportunistic infections to include atypical mycobacteriosis (M. avium/intracellulare). This major opportunist in human AIDS has not been seen in individually caged SIV-infected animals, although it was a common pathogen in an SIV epizootic in outdoor macaques in the 1970's at the CPRC. By understanding the dynamics of spread in groups and by expanding the secondary pathogens seen, we will be able to test potential therapies and vaccines for efficacy in the face of repeated exposures. The third effort described is the development of non-human primate models using monkeys living in Africa. If we are to understand the origin of HIV, we must examine related, naturally occurring viruses in the animal species of origin in its native environment. To do this research we will establish a colony of 18 wild-caught sooty mangabeys at the Liberian Institute for Biomedical Research in Robertsfield, Liberia, West Africa. Serology, SIV isolation and clinical evaluations will be used to determine what strains of SIV are harbored by sooty mangabeys in Africa and what relationship these naturally occurring viruses have to HIV. In another African based study, we will train a scientist from the Institute for Primate Research (IPR) in the detection of SIV and in immunological assays on their group of spontaneously SIV-infected AGMs at the IPR in Kenya.